Hemofiltration systems, methods and devices for treatment of chronic and acute diseases

• US 20050029193A1
• Filed: 05/12/2004
• Published: 02/10/2005
• Est. Priority Date: 03/24/2000
• Status: Active Grant

• Current Assignee: Immunocept Medical Products, LLC (LMF Acquisition Opportunities, Inc.)
• Original Assignee: Immunocept LLC
• Inventors: Matson, James R.
• Granted Patent: US 7,291,122 B2
• Time in Patent Office: Days
• US Class Current: 210/645
• CPC Class Codes: A61M 1/342 Adding solutions to the blood, e.g. substitution solutions for preventing coagulation A61M1/3672
• CPC Class Codes: A61M 1/3437 downstream of the filter, e.g. post-dilution with filtrate
• CPC Class Codes: A61M 1/3441 Substitution rate control as a function of the ultrafiltration rate
• CPC Class Codes: A61M 1/3455 Substitution fluids
• CPC Class Codes: A61M 1/3468 using treated filtrate as substitution fluid
• CPC Class Codes: A61M 1/3472 with treatment of the filtrate
• CPC Class Codes: A61M 1/3486 Biological, chemical treatment, e.g. chemical precipitation; treatment by absorbents

Abstract

A hemofiltration system and method to treat an Inflammatory Mediator Related Disease in a mammal, including chronic and acute diseases, include a hemofilter and an adsorptive device. The hemofilter removes ultrafiltrate from a blood stream extracted from the mammal to create a filtered blood stream and an ultrafiltrate stream. The adsorptive device may include one or more adsorbent materials and may be used to adsorb inflammatory mediators from the ultrafiltrate stream received from the hemofilter to create a post adsorption ultrafiltrate stream. The post adsorption ultrafiltrate stream may be selectively combined with the filtered blood stream and together with the filtered blood stream may be returned to the mammal.

Claims

1. A method for treating a chronic disease in a mammal comprising:

pumping blood from the mammal using a blood pump;

transferring the blood from the blood pump to a hemofilter;

removing an ultrafiltrate from the blood using the hemofilter to create a filtered blood stream and an ultrafiltrate stream;

transferring the ultrafiltrate stream from the hemofilter to an adsorptive device containing at least one fixed adsorbent material;

selectively removing an inflammatory mediator which causes an Inflammatory Mediator Related Disease from the ultrafiltrate stream using the adsorbent material to create a post adsorption ultrafiltrate stream;

combining at least a portion of the post adsorption ultrafiltrate stream with the filtered blood stream and returning the combined post adsorption ultrafiltrate stream and the filtered blood stream to the mammal; and

transferring a portion of the post adsorption ultrafiltrate stream which is not returned to the mammal to a waste reservoir.

2. The method of claim 1 further comprising transferring the post adsorption ultrafiltrate stream from the adsorptive device using an ultrafiltrate pump.

3. The method of claim 1 further comprising:

transferring the post adsorption ultrafiltrate stream from the adsorptive device using a first ultrafiltrate pump; and

transferring any portion of the post adsorption ultrafiltrate stream which is not returned to the mammal to the waste reservoir using a second ultrafiltrate pump.

4. The method of claim 1, wherein the Inflammatory Mediator Related Disease further comprises a Systemic Inflammatory Response Syndrome, a Multiple Organ Dysfunction Syndrome, a Multiple Organ System Failure, or a Compensatory Anti-inflammatory Response Syndrome.

5. The method of claim 1, further comprising the Inflammatory Mediator Related Disease selected from a group consisting of:

Lupus erythematosis, Hemolytic Uremic Syndrome, Bullous Pemphigoid, pemphigus vulgaris, sepsis, fibromyalgia, rheumatoid conditions, chronic neuromuscular diseases, multiple sclerosis, Guillain-Barre syndrome, cryobulinemic vasculitis, chronic inflammatory demyelinating polyneuropathy, macular degeneration, chronic neuromuscular and multifocal motor neuropathy, coagulation disorders, and any combination thereof.

6. The method of claim 1, further comprising the providing at least one therapeutic agent to the blood.

7. A method for treating an Inflammatory Mediator Related Disease in a mammal comprising:

performing hemofiltration on blood from the mammal using a hemofilter to generate an ultrafiltrate;

transferring the ultrafiltrate to an adsorptive device containing at least one fixed adsorbent material;

selectively removing an inflammatory mediator which causes the Inflammatory Mediator Related Disease from the ultrafiltrate using the adsorbent material to create a post adsorption ultrafiltrate;

returning at least a portion of the post adsorption ultrafiltrate to the mammal.

8. The method of claim 7, wherein the Inflammatory Mediator Related Disease further comprises a chronic disease.

9. The method of claim 7, wherein the Inflammatory Mediator Related Disease further comprises an acute disease.

10. The method of claim 7, wherein the Inflammatory Mediator Related Disease further comprises a Systemic Inflammatory Response Syndrome, a Multiple Organ Dysfunction Syndrome, a Multiple Organ System Failure, or a Compensatory Anti-inflammatory Response Syndrome.

11. The method of claim 7, further comprising the Inflammatory Mediator Related Disease selected from a group consisting of:

Lupus erythematosis, Hemolytic Uremic Syndrome, Bullous Pemphigoid, pemphigus vulgaris, sepsis, fibromyalgia, rheumatoid conditions, chronic neuromuscular diseases, multiple sclerosis, Guillain-Barre syndrome, cryobulinemic vasculitis, chronic inflammatory demyelinating polyneuropathy, macular degeneration, chronic neuromuscular and multifocal motor neuropathy, coagulation disorders, and any combination thereof.

12. The method of claim 7, further comprising providing at least one therapeutic agent to the blood.

13. The method of claim 12, wherein the therapeutic agent comprises a biological agent.

14. The method of claim 12, wherein the therapeutic agent comprises a pharmaceutical agent.

15. The method of claim 12, wherein the therapeutic agent further comprises protein C or a protein C derivative.

16. The method of claim 15, further comprising the protein C or protein C derivative selected from a group consisting of:

recombinant activated protein C, human protein C, proteolytic, amidolytic and esterolytic protein C, and any combination thereof.

17. The method of claim 15, further comprising the therapeutic agent selected from a group consisting of:

monoclonal antibodies, receptor antagonists, anti-tumor necrosis factor, interleukin 1 receptor antagonists, endotoxin antibodies, allopurinol, elastase inhibitors, prostaglandin inhibitors, and any combination thereof.

18. A method for treating an Inflammatory Mediator Related Disease in a mammal comprising:

receiving blood from the mammal;

filtering the blood using a hemofilter to remove an inflammatory mediator from the blood; and

providing at least one therapeutic agent to the blood to reduce adverse inflammatory mediator effects associated with treating the Inflammatory Mediator Related Disease.

19. The method of claim 18, wherein the Inflammatory Mediator Related Disease further comprises a Systemic Inflammatory Response Syndrome, a Multiple Organ Dysfunction Syndrome, a Multiple Organ System Failure, or a Compensatory Anti-inflammatory Response Syndrome.

20. The method of claim 18, wherein the Inflammatory Mediator Related Disease further comprises an acute disease.

21. The method of claim 18, wherein the Inflammatory Mediator Related Disease further comprises a chronic disease.

22. The method of claim 18 wherein the therapeutic agent comprises a biological agent.

23. The method of claim 18, wherein the therapeutic agent comprises a pharmaceutical agent.

24. The method of claim 18, further comprising the therapeutic agent selected from a group consisting of:

protein C, derivatives of protein C, recombinant activated protein C, human protein C, proteolytic, amidolytic and esterolytic protein C, monoclonal antibodies, receptor antagonists, anti-tumor necrosis factor, interleukin 1 receptor antagonists, endotoxin antibodies, allopurinol, elastase inhibitors, prostaglandin inhibitors, and any combination thereof.

25. A hemofiltration system to treat a chronic disease in a mammal comprising:

a hemofilter operable to remove an ultrafiltrate from a blood stream extracted from the mammal and to create a filtered blood stream and an ultrafiltrate stream; and

an adsorptive device containing at least one adsorbent material operable to receive the ultrafiltrate stream from the hemofilter and to remove an inflammatory mediator therefrom to create a post adsorption ultrafiltrate stream;

the adsorbent material selected from a group consisting of;

coated materials, uncoated materials, a matrix of rods, a matrix configured for convenient presentation of ultrafiltrate to adsorbent material, beads, particulates, and any combination thereof.

26. The system of claim 25, further comprising a large pore hemofilter.

27. The system of claim 25, further comprising the hemofilter having a membrane with at least one pore having a pore size selected to be larger than a peptide or protein in the blood stream.

28. The system of claim 25, further comprising the hemofilter having a membrane with at least one pore having a pore size larger than approximately 69,000 Daltons.

29. The System of claim 25, further comprising the hemofilter having a membrane with at least one pore having a pore size larger than approximately 100,000 Daltons.

30. The system of claim 25, further comprising the hemofilter operable to remove molecules ranging from 100,000 to 150,000 Daltons in size from the blood stream.

31. The system of claim 25, further comprising the hemofilter having hollow fibers or parallel fibers.

32. The system of claim 25, wherein the hemofilter comprises a membrane and a jacket, further comprising:

the membrane including a material selected from a group consisting of;

polysulfone, polyacrylonitrile, polymethylmethacrylate, polyvinyl-alcohol, polyamide, polycarbonate, cellulose, cellulose derivatives, and any combination thereof; and

the jacket including polycarbonate.

33. The system of claim 25, further comprising the adsorbent material selected from a group consisting of:

silica, activated charcoal, nonionic or uncharged resins or polymers, ionic or charged resins or polymers, anion exchange resins or polymers, cation exchange resins or polymers, neutral exchange resins or polymers, immobilized polymyxin B, immobilized monoclonal antibodies, immobilized inflammatory mediator receptors, immobilized specific antagonists, cellulose, cellulose derivatives, synthetic materials, polysulfone, polyacrylonitrile, polymethylmethacrylate, polyvinyl-alcohol, polyamide, polycarbonate, polystyrene-derivative fibers, Xigris®

, and any combination thereof.

34. The system of claim 25, wherein the ultrafiltrate stream comprises plasma water, electrolytes, and blood peptides and proteins.

35. The system of claim 25, further comprising tubing for use in combining the post adsorption ultrafiltrate stream with the filtered blood stream and returning the combined stream to the mammal.

36. The system of claim 25, further comprising means for selectively combining the post adsorption ultrafiltrate stream with the filtered blood stream and returning the combined stream to the mammal.

37. A hemofiltration system to treat a chronic disease in a mammal comprising:

a blood pump to pump blood from the mammal;

a first tubing to transfer the blood from the mammal to the blood pump;

a hemofilter to receive the blood, the hemofilter operable to remove an ultrafiltrate from the blood to create a filtered blood stream and an ultrafiltrate stream;

a second tubing to transfer the blood from the blood pump to the hemofilter;

a third tubing to transfer the filtered blood stream from the hemofilter to the mammal;

an adsorptive device containing at least one fixed adsorbent material to receive the ultrafiltrate stream from the hemofilter;

the adsorbent material operable to remove an inflammatory mediator that causes an Inflammatory Mediator Related Disease from the ultrafiltrate stream to create a post adsorption ultrafiltrate stream;

a fourth tubing to transfer the ultrafiltrate stream from the hemofilter to the adsorptive device;

means for selectively combining the post adsorption ultrafiltrate stream with the filtered blood stream and returning the combined stream of post adsorption ultrafiltrate and the filtered blood to the mammal including a fifth tubing to transfer the post adsorption ultrafiltrate stream from the adsorptive device;

a sixth tubing to transfer the combined stream of post adsorption ultrafiltrate and the filtered blood to the mammal; and

a seventh tubing to transfer any of the post adsorption ultrafiltrate which is not combined with the filtered blood to a waste reservoir.

38. A hemofiltration system to treat a chronic disease in a mammal comprising:

a hemofilter to receive blood removed from the mammal, the hemofilter operable to remove an ultrafiltrate from the blood removed from the mammal to create filtered blood;

an adsorptive device containing at least one fixed adsorbent material to receive the ultrafiltrate removed from the blood removed from the mammal, the adsorbent material operable to remove an inflammatory mediator that causes an Inflammatory Mediator Related Disease from the ultrafiltrate to create post adsorption ultrafiltrate;

the adsorbent material selected from a group consisting of;

coated materials, uncoated materials, a matrix of rods, a matrix configured for convenient and effective presentation of ultrafiltrate to adsorbent materials, beads, particulates, and any combination thereof;

means for combining at least a portion of the post adsorption ultrafiltrate with at least a portion of the filtered blood and returning the combined post adsorption ultrafiltrate and the filtered blood to the mammal; and

means for discarding any portion of the post adsorption ultrafiltrate and any portion of the filtered blood which is not returned to the mammal.

39. A hemofiltration system to treat a chronic disease in a mammal comprising:

a blood pump to pump a blood stream from the mammal;

a hemofilter operable to remove ultrafiltrate from the blood stream extracted from the mammal and to create a filtered blood stream and an ultrafiltrate stream;

an adsorptive device containing at least one adsorbent material operable to receive the ultrafiltrate stream from the hemofilter and to an inflammatory mediator therefrom to create a post adsorption ultrafiltrate stream;

means for selectively combining the post adsorption ultrafiltrate stream with the filtered blood stream along with returning the combined stream to the mammal to treat an Inflammatory Mediator Related Disease;

a first tubing to transfer the combined stream to the mammal;

a second tubing to transfer any of the post adsorption ultrafiltrate stream which is not returned to the mammal to a waste reservoir;

at least a first ultrafiltrate pump operably coupled with the adsorptive device to assist with transferring the post adsorptive ultrafiltrate stream from the adsorptive device; and

at least a second ultrafiltrate waste pump operably coupled with the second tubing to assist with transferring any of the post adsorption ultrafiltrate stream which is not returned to the mammal to the waste reservoir.

40. A hemofiltration system to treat an Inflammatory Mediator Related Disease in a mammal comprising:

a hemofilter operable to remove an ultrafiltrate from a blood stream extracted from the mammal; and

an adsorptive device containing at least one adsorbent material operable to receive the ultrafiltrate from the hemofilter and to remove an inflammatory mediator therefrom to create a post adsorption ultrafiltrate.

41. The system of claim 40, further comprising the adsorbent material selected from a group consisting of:

coated materials, uncoated materials, a matrix of rods, a matrix configured for convenient presentation of ultrafiltrate to adsorbent material, beads, particulates, and any combination thereof.

42. The system of claim 40, wherein the Inflammatory Mediator Related Disease further comprises an acute disease.

43. The system of claim 40, wherein the Inflammatory Mediator Related Disease further comprises a chronic disease.

44. The system of claim 40, further comprising a large pore hemofilter.

45. The system of claim 40, further comprising the hemofilter having a membrane with at least one pore having a pore size selected to be larger than a peptide or protein in the blood stream.

46. The system of claim 40, further comprising the hemofilter having a membrane with at least one pore having a pore size larger than approximately 69,000 Daltons.

47. The System of claim 40, further comprising the hemofilter having a membrane with at least one pore having a pore size larger than approximately 100,000 Daltons.

48. The system of claim 40, further comprising the hemofilter operable to remove molecules ranging from 100,000 to 150,000 Daltons in size from the blood stream.

49. The system of claim 40, further comprising the hemofilter having hollow fibers or parallel fibers.

50. The system of claim 40, wherein the hemofilter comprises a membrane and a jacket, further comprising:

the membrane including a material selected from a group consisting of;

polysulfone, polyacrylonitrile, polymethylmethacrylate, polyvinyl-alcohol, polyamide, polycarbonate, cellulose, cellulose derivatives, and any combination thereof; and

the jacket including polycarbonate.

51. The system of claim 40, further comprising the adsorbent material selected from a group consisting of:

silica, activated charcoal, nonionic or uncharged resins or polymers, ionic or charged resins or polymers, anion exchange resins or polymers, cation exchange resins or polymers, neutral exchange resins or polymers, immobilized polymyxin B, immobilized monoclonal antibodies, immobilized inflammatory mediator receptors, immobilized specific antagonists, cellulose, cellulose derivatives, synthetic materials, polysulfone, polyacrylonitrile, polymethylmethacrylate, polyvinyl-alcohol, polyamide, polycarbonate, polystyrene-derivative fibers, Xigris®

, and any combination thereof.

52. The system of claim 40, wherein the ultrafiltrate stream comprises plasma water, electrolytes, and blood peptides and proteins.

53. The system of claim 40, further comprising tubing for use in combining the post adsorption ultrafiltrate stream with the filtered blood stream and returning the combined stream to the mammal.

54. The system of claim 40, further comprising means for selectively combining the post adsorption ultrafiltrate stream with the filtered blood stream and returning the combined stream to the mammal.

55. The system of claim 40, further comprising at least one therapeutic agent used in association with the hemofilter to treat the Inflammatory Mediator Related Disease.

56. The system of claim 55, further comprising the therapeutic agent selected from a group consisting of:

recombinant activated protein C, human protein C, proteolytic, amidolytic and esterolytic protein C, and any combination thereof.

57. The system of claim 55, further comprising the therapeutic agent selected from a group consisting of:

monoclonal antibodies, receptor antagonists, anti-tumor necrosis factor, interleukin 1 receptor antagonists, endotoxin antibodies, allopurinol, elastase inhibitors, prostaglandin inhibitors, and any combination thereof.

58. A hemofiltration system for treating an Inflammatory Mediator Related Disease in a mammal comprising:

a hemofilter operable to receive blood from a mammal and to selectively remove an inflammatory mediator from the blood;

at least one therapeutic agent used in association with the hemofilter to treat the Inflammatory Mediator Related Disease; and

the therapeutic agent operable to reduce adverse effects of the inflammatory mediator.

59. The system of claim 58, further comprising the therapeutic agent selected from a group consisting of:

recombinant activated protein C, human protein C, proteolytic, amidolytic and esterolytic protein C, and any combination thereof.

60. The system of claim 58, further comprising the therapeutic agent selected from a group consisting of:

monoclonal antibodies, receptor antagonists, anti-tumor necrosis factor, interleukin 1 receptor antagonists, endotoxin antibodies, allopurinol, elastase inhibitors, prostaglandin inhibitors, and any combination thereof.

61. The system of claim 58, wherein the therapeutic agent further comprises a biological agent.

62. The system of claim 58, wherein the therapeutic agent further comprises a pharmaceutical agent.

63. The system of claim 58, wherein the hemofilter comprises a 100 to 150 kiloDalton hemofilter.